Headache syndromes such as migraine are among the most common of all medical problems, but their causes are poorly understood. The headaches that accompany intracranial pathologies as well as the headache of migraine are thought to result from activation or sensitization of sensory nerve fibers in the intracranial meninges. Neurons in the meningeal sensory pathway have been the subject of numerous neurophysiological studies. However, no one has studied the neurons under conditions that cause headache in humans. During the past project period; we have developed methods for studying changes in activity and mechanosensitivity of dural primary afferent neurons over period of several hours. We now propose to use these methods to study the neurons during the development of two conditions that are associated with headache in humans: meningitis, and nitric oxide-induced migraine headache. Single unit recording will be used to study the discharge properties of these neurons in anesthetized rats. Changes in single neurons will be studied during the development of experimental meningitis, and during the changes induced by application of nitric oxide donors. This information is critically important for establishing the role of these neurons in headache, and for identifying the types of changes in neural activity that might contribute to headache. This information can then be used to develop strategies for blocking the neural changes that result in headache. [unreadable] [unreadable]